Background: Vitamin D (VD) may increase sirtuin 1 (SIRT1) and subsequently PPAR-γ coactivator 1α (PGC-1α) and irisin levels and these improvements may reduce insulin resistance (IR). The aim was to assess the effects of vitamin D supplementation on SIRT1, irisin, and IR in overweight/obese type 2 diabetes (T2D) patients. Methods: Ninety T2D males and females were recruited as a clinical trial study (mean of age and body mass index (BMI) of intervention and placebo groups were 50.05 ± 10.17 and 50.36 ± 10.2 yrs. and 31.37 ± 3.4 and 30.43 ± 3.2 kg/m 2 , respectively). The inclusion criteria were T2D, VD deficient, BMI > 25 kg/m 2 , and serum HbA1c < 8.5%. The exclusion criteria were using vitamin and mineral supplements, having any acute disease, recent modifying dose or type of drugs. The supplementation was 50,000 IU/week VD or placebo for 8 weeks. The demographic characteristics, anthropometrics, dietary intakes and physical activity status, sun exposure status, fasting blood sugar (FBS) and insulin, glycosylated hemoglobin (HbA1c), irisin, SIRT1, 25-hydroxy D3 (25(OH)VD), homeostasis model assessment of insulin resistance (HOMA-IR), and quantitative insulin sensitivity check index (QUICKI) were determined. The significant P-value was ≤0.05. Results: The increase of serum VD, SIRT1, and irisin in the intervention group was significant (p < 0.001). HbA1c was decreased significantly by 1%. The changes in the other glucose indices (FBS, insulin, and IR) were non-significant. Conclusions: VD supplementation may improve T2D by decreasing HbA1c and increasing SIRT1 and irisin in VD deficient T2D patients. Further trials are suggested. Trial registration: Iranian Registry of Clinical Trials, IRCT201604202365N11. Registered 21/08/2016, http://en.irct. ir/trial/2019.

Background: According to the recent studies, vitamin D deficiency has been correlated with progress in type 2 Diabetes and Metabolic Syndrome. The aim of this study was to assess the effect of vitamin D supplementation on glucose and lipid profiles, blood pressure, and biomarkers of liver and kidney in type 2 diabetic patients. Methods: In this Double blinded randomized clinical trial, 90 patients with type 2 diabetes and serum 25-Hydroxy vitamin D levels of less than 30 ng/ml recruited from "Besat Diabetes Clinic" in Rasht, North of Iran. The subjects took 50000 IU vitamin D supplements or placebo for 8 weeks. We assessed the levels of serum 25 (OH) vitamin D, glucose and lipid profiles, oxidative and inflammatory indices, liver and kidney biomarkers, blood pressure, and sun exposure time, physical activity before and after intervention, and compared them between cases and controls. Results: Vitamin D supplementation significantly increased serum vitamin D level, Superoxide Dismutase (SOD) activity, and significantly decreased serum HbA1C (Glycosylated Hemoglobin) level (p<0.001). High Density Lipoprotein (HDL) Cholesterol increased significantly (p=0.016), and Erythrocyte Sedimentation Rate (ESR) significantly decreased (p=0.039) after the intervention. Conclusion: Our results represented that weekly supplementation with 50000 IU vitamin D for 8 weeks may be effective by improving HbA1C and lipid profile in type 2 diabetes mellitus.